TY - JOUR
T1 - The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity
AU - Kaur, Harpreet
AU - Hütt-Cabezas, Marianne
AU - Weingart, Melanie F.
AU - Xu, Jingying
AU - Kuwahara, Yasumichi
AU - Erdreich-Epstein, Anat
AU - Weissman, Bernard E.
AU - Eberhart, Charles G.
AU - Raabe, Eric H.
N1 - Publisher Copyright:
© 2015 by the American Association of Neuropathologists, Inc.
PY - 2015/2/2
Y1 - 2015/2/2
N2 - Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central nervous system tumor. The poor prognosis of AT/RT warrants identification of novel therapeutic targets and strategies. High-mobility Group AT-hook 2 (HMGA2) is a developmentally important chromatin-modifying protein that positively regulates tumor growth, self-renewal, and invasion in other cancer types. High-mobility group A2 was recently identified as being upregulated in AT/RT tissue, but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short-hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2 led to decreased cell growth, proliferation, and colony formation and increased apoptosis. We also found that suppression of HMGA2 negatively affected in vivo orthotopic xenograft tumor growth, more than doubling median survival of mice from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these lethal pediatric tumors.
AB - Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central nervous system tumor. The poor prognosis of AT/RT warrants identification of novel therapeutic targets and strategies. High-mobility Group AT-hook 2 (HMGA2) is a developmentally important chromatin-modifying protein that positively regulates tumor growth, self-renewal, and invasion in other cancer types. High-mobility group A2 was recently identified as being upregulated in AT/RT tissue, but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short-hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2 led to decreased cell growth, proliferation, and colony formation and increased apoptosis. We also found that suppression of HMGA2 negatively affected in vivo orthotopic xenograft tumor growth, more than doubling median survival of mice from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these lethal pediatric tumors.
KW - Atypical teratoid/rhabdoid tumor
KW - High-mobility group AT-hook 2
KW - INI1
KW - Malignant rhabdoid tumor
KW - Pediatric brain tumor
KW - SNF5.
KW - let-7
UR - http://www.scopus.com/inward/record.url?scp=84921930622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921930622&partnerID=8YFLogxK
U2 - 10.1097/NEN.0000000000000161
DO - 10.1097/NEN.0000000000000161
M3 - Article
C2 - 25575139
AN - SCOPUS:84921930622
SN - 0022-3069
VL - 74
SP - 177
EP - 185
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 2
ER -